Control of Blood Glucose and Cardiovascular Risk Profile

A large number of epidemiological studies identified diabetes as an independent risk factor for cardiovascular (CV) events, the excess risk being proportional to blood glucose levels. Based on these data, several large randomized clinical trials (RCTs) were initiated to evaluate whether better glycemic control obtained with medications would lead to a lower incidence of CV events. Although results of the single RCTs were inconsistent, meta-analytic evidence suggests that the achievement of a more ambitious glycemic target is able to reduce both micro- and macro-vascular complications, and that this protective effect is evident only if patients are followed for a long period of time (~10 years). It also became clear that apart from the achieved glycemic levels, the use of specific medications could have an impact on CV outcomes. Regulatory agencies started to request that in order to receive approval for commercialization, candidate drugs for the treatment of type 2 diabetes had to have a safe CV profile. As a consequence, a considerable number of CV safety trials were conducted with several classes of drugs. Among them, sodium-glucose transporter 2 inhibitors (SGLT2-i) and glucagon like peptide 1 receptor agonists (GLP1-RA) were able to reduce the incidence of CV events compared with placebo, an effect that was largely independent from their glucose-lowering ability. These results profoundly changed clinical practice guidelines from international societies, which now recommend the use of these drugs independently from glycemic control for their protective properties on CV and renal outcomes.